Gasket for syringe and syringe having gasket

ABSTRACT

A gasket for use in a syringe so formed as to liquid-tightly and slidably contact an inner surface of an outer cylinder of the syringe, the gasket including a gasket body made of an elastic body and a coating layer formed on a portion thereof which contacts at least the syringe, wherein the coating layer includes a composition containing a silicone resin which includes a condensate of a reactive silicone resin having a terminal silanol group and which has a siloxane bond derived from the silanol group, and does not contain solid fine particles.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.12/824,773 filed Jun. 28, 2010, which is a continuation of InternationalApplication No. PCT/JP2008/073767 filed on Dec. 26, 2008, which in turnclaims priority to Japanese Application No. 2007-339649 filed on Dec.28, 2007, the entire contents of which are incorporated herein byreference.

TECHNOLOGICAL FIELD

The present invention relates to a gasket for use in a syringe having arelatively stable sliding performance and a syringe having the gasket.

BACKGROUND

A prefilled syringe in which a liquid medicine is filled in advance hasbeen conventionally used to prevent use of a mix-up of medicine, preventhospital infection, disposability, and increase efficiency in hospitalservice. A syringe including a syringe to be used as the prefilledsyringe can be constructed of an outer cylinder, a gasket slidableinside the syringe, and a plunger for operating the movement of thegasket. To enhance the sliding performance of the gasket and obtain ahigh degree of flow accuracy without generating a large irregularity inthe discharge of the liquid medicine, silicone oil or the like isapplied to a sliding portion of the outer surface of the gasket or theinner surface of the syringe as a lubricant. Depending on the kind of aliquid medicine that is used, an interaction can occur between theliquid medicine and the lubricant such as the silicone oil. When theliquid medicine is stored for a long time after the liquid medicine isfilled in the syringe, the liquid medicine can be denatured by theinteraction. Thus, it is difficult to use some kinds of medicines with aprefilled syringe.

The prefilled syringe to be stored for a long time with the liquidmedicine filled therein can be beneficial for keeping the liquidmedicine stable and eliminate the need for the lubricant.

To solve the above-described problem, as disclosed in a patent document1 (Japanese Patent Publication Laid-Open No. 62-32970) and a patentdocument 2 (Japanese Patent Publication Laid-Open No. 2002-089717, U.S.Pat. No. 7,111,848), prefilled syringes were proposed in which thesurface of the gasket is covered with the fluorine resin which is amaterial having a lower friction coefficient than the material of thegasket body to eliminate the use of the lubricant.

The present applicant proposed the gasket having the coating layercomposed of the fluorine resin, the silicon resin, and the urethaneresin, as disclosed in a patent document 3 (Japanese Patent PublicationLaid-Open No. 2004-321614); and the gasket having the coating layercomposed of the film made of the composition containing the slidingproperty-imparting component and the flexibility-imparting component andof the fine particles held by the film to form the rough surface on thegasket, as disclosed in a patent document 4 (Japanese Patent PublicationLaid-Open No. 2006-167110).

Patent document 1: Japanese Patent Publication Laid-Open No. 62-32970

Patent document 2: Japanese Patent Publication Laid-Open No.2002-089717, U.S. Pat. No. 7,111,848

Patent document 3: Japanese Patent Publication Laid-Open No. 2004-321614

Patent document 4: Japanese Patent Publication Laid-Open No. 2006-167110

The gaskets disclosed in the patent document 1 (Japanese PatentPublication Laid-Open No. 62-32970) and the patent document 2 (JapanesePatent Publication Laid-Open No. 2002-089717, U.S. Pat. No. 7,111,848)are expected to be effective in dependence on a use condition. But in apreparation for a prefilled syringe demanded to discharge the liquidmedicine under a high pressure and have the performance of stablydischarging the liquid medicine little by little with a very highaccuracy for a long time by using a syringe pump or the like,liquid-tightness and sliding performance which are fundamentalperformance demanded for the syringe are still in a trade-offrelationship. A syringe which allows these performances to be compatiblewith each other at a high level and has a higher performance is needed.

That is, in administration of the liquid medicine by using the syringepump, when the liquid medicine is discharged in a condition where theflow rate is so low that the flow of the liquid medicine is invisible(for example, in the syringe having a diameter of about 24 mm, a movingspeed of a gasket when it is made to discharge in 1 mL/hour is about 2mm/hour), an unstable discharge state called pulsation is liable tooccur. Thus there is a fear that accurate administration of the liquidmedicine is prevented.

The gaskets disclosed in the patent document 3 (Japanese PatentPublication Laid-Open No. 2004-321614) and the patent document 4(Japanese Patent Publication Laid-Open No. 2006-167110) are liquid-tightand have stable sliding performance without applying a lubricant to thesliding surface thereof. But in the former, materials forming thecoating layer are used in a wide variety and hence the former hasproblems in terms of production and cost. The latter has a problem thatfine particles held by the coating layer cause the formation of thecoating layer to be difficult.

SUMMARY

Exemplary aspects of a gasket and syringe have been developed to providean improved gasket and syringe. For example, according to exemplaryaspects, a gasket having relatively stable sliding performance withoutapplying a lubricant to a sliding surface thereof and a syringe havingthe gasket, are provided.

Exemplary aspects are as follows:

A gasket for use in a syringe so formed as to liquid-tightly andslidably contact an inner surface of an outer cylinder of the syringe.The gasket comprises a gasket body made of an elastic body and a coatinglayer formed on a portion thereof which contacts at least the syringe.The coating layer comprises a composition containing silicone resinwhich comprises a condensate of reactive silicone having a terminalsilanol group, and wherein the condensate contains a siloxane bondderived from the silanol group. The coating layer does not contain solidfine particles.

Also provided is a syringe that has an outer cylinder, theabove-described gasket slidably accommodated inside the outer cylinder,and a plunger which has been mounted on the gasket or can be mountedthereon.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a front view showing a gasket of an exemplary embodiment.

FIG. 2 is a sectional view of the gasket shown in FIG. 1, according toan exemplary embodiment.

FIG. 3 is a plan view of the gasket shown in FIG. 1, according to anexemplary embodiment.

FIG. 4 is a bottom view of the gasket shown in FIG. 1, according to anexemplary embodiment.

FIG. 5 is a sectional view of a prefilled syringe in which the gasketshown in FIG. 1 is used, according to an exemplary embodiment.

FIG. 6 shows results of the discharge characteristic of a syringe,according to an exemplary embodiment.

FIG. 7 shows results of the discharge characteristic of a syringe of acomparison example.

DETAILED DESCRIPTION

A gasket of an exemplary embodiment is described below. The gasket 1slidably contacts an inner surface of an outer cylinder (barrel) of asyringe and has a coating layer 3 formed on a portion thereof whichcontacts the syringe. The coating layer 3 is composed of a compositioncontaining a specific silicone resin which is described later.

A gasket of an exemplary embodiment is described below, in which thegasket is used for and applied to the syringe.

The gasket 1 of this embodiment can be used for a syringe andliquid-tightly and slidably accommodated inside an outer cylinder 11.The gasket 1 has the coating layer 3 disposed on a portion thereof whichcontacts the outer cylinder 11. The coating layer 3 contains thespecific silicone resin to be described later. The gasket 1 has a corepart 2 and the coating layer 3 formed on a portion, of at least an outersurface of the core part 2, which contacts the inner surface of theouter cylinder 11. The coating layer 3 may be formed on the entire outersurface of the core part 2.

As shown in FIGS. 1, 2, and 5, the core part 2 of the gasket 1 for usein the syringe has a main body 5 extending in an almost equal diameter;a tapered portion 6, disposed at a distal side of the main body 5, whosediameter decreases taperingly to the distal end thereof; aplunger-mounting portion 4 provided inside the main body 5 from aproximal end thereof toward a distal side thereof; a distal-side annularrib 7 a provided on a side surface of the distal portion of the mainbody 5; and a proximal-side annular rib 7 b provided on a side surfaceof the proximal portion of the main body 5. As shown in FIGS. 2 and 4,the plunger-mounting portion 4 is formed as an approximately columnarconcave portion which is disposed inside the main body 5 and extendsfrom the proximal end of the main body 5 to a position in the vicinityof the distal end thereof. A screwing portion 8 capable of engaging ascrewing portion formed at a distal end of a plunger is formed on a sidesurface of the concave portion. A distal-end surface of the concaveportion is formed almost flatly. The plunger-mounting portion 4 does notnecessarily have to be formed as the screwing portion, but may be formedas an engaging portion which engages the distal portion of the plunger.

The outer diameters of the annular ribs 7 a and 7 b are formed a littlelarger than the inner diameter of the outer cylinder 11 for use in thesyringe. Therefore the annular ribs 7 a and 7 b compressively deforminside the outer cylinder 11. In the embodiment, two annular ribs areformed, but one or three or more annular ribs may be formed.

As a material composing the core part 2, an elastic material can beused. The elastic material is not limited to a specific one, but rubbermaterials (specifically, vulcanized rubber materials) such as naturalrubber, isoprene rubber, butyl rubber, chloroprene rubber,nitrile-butadiene rubber, styrene-butadiene rubber, and silicone rubber;styrene elastomer and hydrogenated styrene elastomer; and mixtures ofthe styrene elastomer and polyolefins such as polyethylene,polypropylene, polybutene, and α-olefin copolymers; mixtures of thestyrene elastomer and oil such as liquid paraffin, process oil; andmixtures of the styrene elastomer and powdery inorganic substances suchas talc, cast, mica, and the like are listed. Further it is possible touse a polyvinyl chloride elastomer, an olefin elastomer, a polyesterelastomer, a polyamide elastomer, a polyurethane elastomer, and mixturesof these elastomers as materials composing the core part 2. As thecomposing material, the diene rubbers and the styrene elastomer arepreferable because these rubbers and elastomers have elastic propertiesand can be sterilized by γ (gamma) ray, electron beams, andhigh-pressure steam.

In an exemplary embodiment, the coating layer 3 is formed at least atthe portion where the annular ribs are disposed. More specifically, thecoating layer 3 can be formed at the distal-side annular rib 7 a and theproximal-side annular rib 7 b. The thickness of the coating layer 3 canbe 1 to 30 μm, for example, 3 to 10 μm. When the thickness of thecoating layer 3 is not less than 1 μm, the coating layer 3 can displaygood slidable performance. When the thickness of the coating layer 3 isnot more than 30 μm, the coating layer 3 does not adversely affect theelasticity of the gasket. In an exemplary embodiment, the coating layer3 does not contain fine particles. Solvent-based silicone resindissolved in an organic solvent and water-based silicone resinemulsified and dispersed in water can be used. But from the viewpoint ofthe influence on the material of the gasket or the aptitude as a liquidmedicine accommodation container, the water-based silicone resin can beused. The coating layer 3 can be constructed of a resin composed of amaterial having a low friction coefficient rather than the elasticmaterial composing the gasket body 1.

The coating layer 3 can be composed of a composition containing areactive silicone resin having a terminal silanol group and does notcontain solid fine particles.

In an exemplary embodiment, the coating layer 3 can be composed of acomposition containing silicone resin which contains or consists of acondensate of the reactive silicone resin having the terminal silanolgroup, wherein the condensate has a siloxane bond derived from a silanolgroup. In an exemplary embodiment, the coating layer 3 does not containsolid fine particles.

The composition containing the reactive silicone resin can be athermosetting silicone resin or room temperature-curing silicone resin.For example, it can be beneficial that the composition containing thereactive silicone resin is the thermosetting silicone resin from thestandpoint of workability and the like.

As the reactive silicone, polydimethylsiloxane having the terminalsilanol group can be used. The reactive silicone can have the silanolgroup at both terminals thereof. When polysiloxane silicone having theterminal silanol group is used as the reactive silicone, the condensateof the reactive silicone has siloxane bonds in its entire main chain.

As the reactive silicone having the terminal silanol group, thepolysiloxane silicone having the silanol group at both terminals thereofcan be used. Both-terminal polydimethylsiloxane silanol, both-terminalpolydiphenylsiloxane silanol, both-terminal diphenylsiloxanesilanol-dimethylsiloxane copolymer can be used. The form of the reactivesilicone is not limited to a specific one, but it is possible to use theabove-described reactive silicone siloxane compounds, polysiloxane,consisting of the condensate of the reactive silicone siloxane compound,which is dispersed, emulsified, and dissolved in an aqueous medium,copolymer emulsion formed by copolymerizing an alkoxysilylgroup-containing vinyl monomer with other vinyl monomer, and emulsionformed by compositing the polysiloxane with an organic polymer.

The resin composition forming the coating layer 3 can contain a secondsilicone compound different from the reactive silicone resin having thesilanol group or the siloxane bond. As the second silicone compound,alkylalkoxysilane, phenylalkoxysilane, alkylphenoxysilane,aminoalkylalkoxysilane, and glycidoxyalkylalkoxysilane can be used.

The composition forming the coating layer 3 can contain thealkylalkoxysilane or the phenylalkoxysilane as the second siliconecompound and the aminoalkylalkoxysilane and/or theglycidoxyalkylalkoxysilane as a third silicone compound.

The resin composition forming the coating layer 3 can contain thealkylalkoxysilane or the phenylalkoxysilane as the second siliconecompound, the aminoalkylalkoxysilane as the third silicone compound, andthe glycidoxyalkylalkoxysilane as a fourth silicone compound.

As the second silicone compound, the alkylalkoxysilane, thealkylphenoxysilane, and the phenylalkoxysilane can be used. Thealkylalkoxysilane has at least one alkyl group having 1 to 20 carbonatoms and at least one alkoxy group having 1 to 4 carbon atoms. As thealkylalkoxysilane, methyltrimethoxysilane, methyltriethoxysilane,methyltriisobutoxysilane, methyltributoxysilane,methylsec-trioctyloxysilane, isobutyltrimethoxysilane,cyclohexylmethyldimethoxysilane, diisopropyldimethoxysilane,propyltrimethoxysilane, diisobutyldimethoxysilane,n-octylmethoxysiloxane, ethyltrimethoxysilane, dimethyldimethoxysilane,octyltriethoxysilane, hexyltrimethoxysilane, hexyltriethoxysilane,octamethylcyclotetrasiloxane, methyltri(acryloyloxyethoxy)silane,lauryltriethoxysilane, stearyltrimethoxysilane, stearyltriethoxysilane,ethyltriethoxysilane, propyltriethoxysilane, butyltriethoxysilane,butyltrimethoxysilane, pentyltrimethoxysilane, pentyltriethoxysilane,heptyltrimethoxysilane, heptyltriethoxysilane, octyltrimethoxysilane,nonyltrimethoxysilane, nonyltriethoxysilane, decyltrimethoxysilane,decyltriethoxysilane, undecyltrimethoxysilane, undecyltriethoxysilane,dodecyltrimethoxysilane, dodecyltriethoxysilane,tridecyltrimethoxysilane, tridecyltriethoxysilane,tetradecyltrimethoxysilane, tetradecyltriethoxysilane,pentadecyltrimethoxysilane, pentadecyltriethoxysilane,hexadecyltrimethoxysilane, hexadecyltriethoxysilane,heptadecyltrimethoxysilane, heptadecyltriethoxysilane,octadecyltrimethoxysilane, octadecyltriethoxysilane,nonadecyltrimethoxysilane, nonadecyltriethoxysilane,eykosiltrimethoxysilane, eykosiltriethoxysilane, can be used.

As the alkylphenoxysilne, methyltriphenoxysilane can be used. As thephenoxyalkoxysilane, phenyltrimethoxysilane, phenyltriethoxysilane,diphenyldimethoxysilane, diphenyldiethoxysilane, can be used.

As the second silicone compound, it is also possible to usemethyltri(glycidyloxy)silane, tri methylchlorosilane, dimethylchlorosilane, methyltrichlorosilane, tetraethoxysilane,heptadecafluorodecyltrimethoxysilane,tridecafluorooctyltrimethoxysilane, tetrapropoxysilane.

As the second silicone compound, the aminoalkylalkoxysilane can be used.As the aminoalkylalkoxysilane, 3-aminopropyltriethoxysilane,3-(2-aminoethyl)aminopropyltrimethoxysilane,3-(2-aminoethyl)aminopropylmethyldimethoxysilane,3-aminopropyltrimethoxysilane, 3-phenylaminopropyltrimethoxysilane, canbe used.

As the second silicone compound, the glycidoxyalkylalkoxysilane can beused. As the glycidoxyalkylalkoxysilane,3-glycidoxypropyltrimethoxysilane, 3-glycidoxypropyltriethoxysilane,3-glycidoxypropylmethyldiethoxysilane,3-glycidoxypropylmethyldimetoxysilane,2-(3,4-epoxycyclohexyl)ethyltrimethoxysilane, can be used.

As the second silicone compound, it is possible to use silane compoundssuch as 3-ureidopropyltriethoxysilane, diaryldimethylsilane,n-octyldimethylchlorosilane, tetraethoxysilane,trifluoropropyltrimethoxysilane.

The composition forming the coating layer 3 can contain the second andthird silicone compounds. The second silicone compound can be selectedfrom among the alkylalkoxysilane, the alkylphenoxysilane, and thephenylalkoxysilane. As the third silicone compound, theaminoalkylalkoxysilane or the glycidoxyalkylalkoxysilane can be used.The composition forming the coating layer 3 can contain the second,third, and fourth silicone compounds. The second silicone compound canbe selected from among the alkylalkoxysilane, the alkylphenoxysilane,and the phenylalkoxysilane. As the third silicone compound, theaminoalkylalkoxysilane can be used. As the fourth silicone compound,glycidoxyalkylalkoxysilane can be used.

In an exemplary embodiment, the coating layer 3 formed on the gasketdoes not contain the “solid fine particle”. The “solid fine particle”herein means a particle having a size to such an extent as to affect theroughness of the outer surface of the coating layer 3 when the coatinglayer 3 is formed. Specifically the “solid fine particle” means aparticle having a diameter larger than 10% of the thickness of thecoating layer 3.

Because the gasket 1 has the above-described coating layer 3, the gasket1 can have a stable sliding performance without applying a lubricant tothe sliding surface thereof and can be capable of maintaining sealingperformance inside the medicine accommodation space. The initial slidingresistance value of the coating layer (in other words, gasket havingcoating layer) can be not more than a maximum value of the dynamicsliding resistance value thereof. The gasket satisfying theabove-described condition can be capable of starting favorable initialsliding and does not make an excessive initial movement.

As the aqueous silicone resin, it is possible to use polysiloxanecomplex aqueous emulsion composed of a crosslinked polymer forming thecore part, a non-crosslinked polymer forming a shell portion coveringthe core part, and polysiloxane disposed in the vicinity of the surfaceof the shell.

An exemplary method of forming the coating layer 3 is described below.In the method of forming the coating layer, a coating solutioncontaining components composing the silicone resin can be mixed with oneanother in amounts. The resulting material can be dispersed andsuspended in purified water. The coating layer can be obtained byapplying the coating solution to the clean surface of the gasket andthereafter curing it. At this time, the coating solution can be appliedto the surface of the gasket by carrying out a known method such as adip coating method, a spraying method, and the like. It can bepreferable to spray the coating solution to the surface of the object tobe coated with the object being rotated (specifically, at 100 to 600rpm). In applying the coating solution to the surface of the gasket byspraying it, it can be preferable to do so after heating the portion ofthe gasket to be coated to 60 to 120 degrees C. The coating solution canbe rapidly fixed to the surface of the portion of the gasket to becoated without water repellence.

As the method of curing the coating solution, it can be left at a normaltemperature, but it can be preferable to harden it by heating it.

The method of thermally curing the coating solution is not limited to aspecific method, provided that the base material of the gasket is notmodified or deformed. It is possible to use conventional methods such ashot air drying and a drying oven using infrared rays or a method ofusing a drier to be operated under a reduced pressure. The thickness ofthe coating layer to be formed can be 1 to 30 μm, for example, 3 to 10μm. Such a coating layer can be easily formed by appropriatelycontrolling the concentration of the mixed solution, the dipping method,and the spraying method.

In preparing the coating solution containing the silicone resin, acatalyst for accelerating thermosetting can be used as an additive.

As the catalyst, acid, alkali, amine, organic salts of metals, titanate,and borate can be used. Organic acid salts such as zinc octylate, ironoctylate or organic acid salts of cobalt, tin, and lead can be used.

As the organic acid salts of tin, it is possible to usebis(2-ethylhexanoate)tin, bis(neodecanoate)tin,di-n-butylbis(2-ethylhexylmalate)tin,di-n-butylbis(2,4-pentanedionate)tin, di-n-(butylbutoxychloro)tin,di-n-(butyldiacetoxy)tin, tin di-n-butyldilaurate, tindimethyldineodecanoate, tin dimethylhidroxy(oleate), and tindioctyldilaurate.

In preparing the coating solution containing the silicone resin,additives such as a surface active agent, alcohol, and the like can beused to uniformly emulsify, suspend, and disperse the coating solution.

As the surface active agent, anion surface active agents can be used.Any of the anion surface active agents can be used. It is possible touse aliphatic monocarboxylate, polyoxyethylene alkyl ether carboxylate,N-acylsarcosinate, N-acyl glutamate, dialkyl sulfosuccinate,alkanesulfonate, alpha olefin sulfonate, straight chainalkylbenzenesulfonate, molecular chain alkylbenzenesulfonate,naphthalene sulfonate-formaldehyde condensate, alkylnaphthalenesulfonate, N-methyl-N-acyltaurine, alkyl sulfate, polyoxyethylenealkylether sulfate, fat sulfate salt, alkyl phosphate, polyoxyethylenealkylether sulfate and polyoxyethylenealkylphenyl ether sulfate.

Nonionic surface active agents can be used. Any of the nonionic surfaceactive agents can be used. It is possible to use polyoxyethylene alkylether, polyoxyalkylene derivatives, polyoxyethylene alkyl phenyl ether,polyoxyethylene sorbitan fatty acid ester, fatty acid alkanolamide,glycerin fatty acid ester, sorbitan fatty acid ester, polyoxyethylenealkylamine, and alkylalkanolamide.

The syringe 10 can have the outer cylinder 11, the gasket 1 slidablyaccommodated inside the outer cylinder 11, and a plunger 17 which hasbeen mounted or can be mounted on the gasket 1.

For example, as shown in FIG. 5, the syringe 10 is constructed of theouter cylinder 11, for use in the syringe, which has a needle-mountingportion 15 disposed at the distal side thereof and a flanges 16 disposedto be opposite at the proximal end thereof; the gasket 1, for use in thesyringe, which is capable of liquid-tightly and airtightly sliding on aninner surface 12 of the outer cylinder 11; the plunger 17 which has beenor can be mounted on the gasket 1 for use in the syringe; a sealingmember 18 for sealing the needle-mounting portion 15 of the outercylinder 11 for use in the syringe; and a medicine-accommodating portion19, for accommodating a medicine 26, which is formed among the sealingmember 18, the inner surface 12 of the outer cylinder 11, and the gasket1 for use in the syringe. Instead of the sealing member 18, a needle maybe mounted on the needle-mounting portion 15. As shown in FIG. 5, thesealing member 18 may be of a type having a piercing portion into whicha double ended needle can be directly inserted or may be of a type inwhich a medicine cannot be discharged until the sealing member isremoved. The gasket 1 has the coating layer 3. In the syringe 10, it canbe preferable that the dynamic sliding resistance value of the gasket 1when the gasket 1 slides at a low speed (100 mm/minute) inside the outercylinder 11 is not more than 20N. Such a low dynamic sliding resistancevalue can be obtained when the gasket 1 has the coating layer 3. Forexample, the dynamic sliding resistance value of the gasket 1 when thegasket 1 slides at the low speed (100 mm/minute) inside the outercylinder 11 can be 1N to 20N.

According to an exemplary aspect, this medical appliance is a prefilledsyringe 25 composed of the syringe 10 and the medicine 26, as shown inFIG. 5.

The outer cylinder 11 for use in the syringe has the needle-mountingportion 15 disposed at the distal portion thereof and the flange 16disposed at the proximal end thereof. The outer cylinder 11 is made of amaterial transparent or semitransparent. The outer cylinder 11 can bemade of a material having a low oxygen permeability or vaporpermeability. The material forming the outer cylinder 11 can have aglass transition point or a melting point not less than 110 degrees C.

As the material forming the outer cylinder 11, various general-purposerigid plastic materials can be used. Polyolefin such as polypropylene,polyethylene, poly(4-methylpentene-1), and cyclic polyolefin; polyesterssuch as polyethylene terephthalate, polyethylene naphthalate, andnon-crystalline polyarylate; polystyrene; polyamide; polycarbonate,polyvinyl chloride; acrylic resin; acrylonitrile-butadiene-styrenecopolymer, and non-crystalline polyetherimide can be used. Thepolypropylene, the poly(4-methylpentene-1), the cyclic polyolefin, thepolyethylene naphthalate, and the non-crystalline polyetherimide can beused because these resins are transparent and resistant to heatsterilization. These resins can be used as materials to form not only asyringe barrel, but also a container capable of accommodating amedicine. It is also possible to use glass as a material to form theouter cylinder.

As shown in FIG. 5, the plunger 17 has a sectionally cross-shaped mainbody 20 extended axially; a plunger-side screwing portion 21, providedat the distal portion thereof, which engages the plunger-mountingportion 4; a disk-shaped gasket-pressing portion provided between theplunger-side screwing portion 21 and the main body 20; a disk portion22, for pressing use, which is disposed at the proximal end of the mainbody 20; and a disk-shaped rib formed midway on the main body 20.

The medicine 26 can be contained inside the syringe 10 of this exemplaryembodiment. As the medicine 26, it is possible to use a solution and asolid agent such as a powdery medicine and a freeze-dried medicine. Whena liquid medicine having poor water solubility and a high adsorbabilityor a liquid medicine containing a surface active agent and having a lowviscosity and a high degree of penetration is accommodated inside thesyringe 10, silicone oil is unnecessary. When the coating layer 3 isprovided at a portion which contacts an accommodated medicine, theadsorption of the medicine can be prevented. Thus it is possible to usethe syringe 10 for the liquid medicine having the above-describedproperties.

As the material composing the plunger 17 and the sealing member 18, hardresin or semi-hard resin can be used such as, for example, polyvinylchloride, high-density polyethylene, polypropylene, polystyrene,polyethylene terephthalate, polycarbonate, acrylic resin, and the like.

EXAMPLES

Examples are described below.

Example 1

By using butyl rubber, the core part of a gasket for use in a syringe,having a configuration shown in FIGS. 1 and 2 was produced. The corepart was formed by press-molding a vulcanizable rubber compositioncomposed of butyl rubber and an additive added thereto. Describing theconfiguration of the obtained core part, it had a length of 20 mm, anouter diameter of 23.7 mm at distal-side and proximal-side annular ribs,a length of 10 mm between the center of the distal-side annular rib andthe center of the proximal-side annular rib, an outer diameter of 21.5mm at an identical diameter portion between the distal-side annular riband the proximal-side annular rib, a length (depth) of 8 mm in theplunger-mounting concave portion having a female screw at an inner sidethereof, an inner diameter of 14.5 mm at the distal side of theplunger-mounting concave portion, and an inner diameter of 15 mm at therear side of the plunger-mounting concave portion.

Thereafter 29 parts by weight of silicone resin and one part by weightof tin dioctyldilaurate were added to 66 parts by weight of purifiedwater to prepare a coating solution. As the silicone resin, substancesshown below were mixed with one another by using straight-chain sodiumalkylbenzene sulfonate.

1) 25 parts by weight of 1501 Fluid (commercial name, produced by DowCorning Toray Co., Ltd.) containing both-terminal polydimethyl siloxanesilanol as its main component.

2) 0.1 parts by weight of Z-6366 (commercial name, produced by DowCorning Toray Co., Ltd.) containing methyltrimethoxysilane as its maincomponent.

3) One part by weight (resin ratio: 50%) of a mixture of Z-6011(commercial name, produced by Dow Corning Toray Co., Ltd.) containing3-aminopropyltriethoxysilane as its main component and an ethanolsolution of maleic anhydride.

4) 0.5 parts by weight of Z-6040 (commercial name, produced by DowCorning Toray Co., Ltd.) containing 3-glycidoxypropyltrimethoxysilane asits main component.

After at a room temperature and a normal pressure, the gasket coremember produced in the above-described manner was heated to 90 degreesC. for 30 minutes, the gasket core member was rotated (300 rpm) on itsaxis with the coating solution having the above-described compositionbeing sprayed to the gasket core member from the side surface of thegasket core member which was rotating. Thereafter the coating solutionwas dried at 150 degrees C. for 30 minutes. Thereby the gasket wasformed. Thereafter to wash extra coating solution which remained on theproduced gasket, cleaning was performed with purified water having atemperature not less than 80 degrees C. The average thickness of acoating layer formed on the surface of the core member was about 8 μm.This gasket was set as the example 1.

Example 2

29 parts by weight of the silicone resin as in the case of the example 1and one part by weight of the tin dioctyldilaurate were added to 66parts by weight of the purified water to prepare a main agent.

Five parts by weight of purified water was added to 8 parts by weight ofthe main agent and both were mixed with each other to prepare a coatingsolution. After at a room temperature and a normal pressure, the gasketcore member produced in the above-described manner was heated to 90degrees C. for 30 minutes, the gasket core member was rotated (300 rpm)on its axis with the coating solution having the above-describedcomposition being sprayed to the gasket core member from the sidesurface of the gasket core member which was rotating. Thereafter thecoating solution was dried at 150 degrees C. for 30 minutes. Thereby thegasket was formed. Thereafter to wash extra coating solution whichremained on the produced gasket, cleaning was performed with purifiedwater having a temperature not less than 80 degrees C. The averagethickness of a coating layer formed on the surface of the core memberwas about 5 μm. This gasket was set as the example 2.

Example 3

29 parts by weight of the silicone resin and one part by weight of thetin dioctyldilaurate were added to 66 parts by weight of the purifiedwater to prepare a coating solution. As the silicone resin, substancesshown below were mixed with one another by using the straight-chainsodium alkylbenzene sulfonate.

1) 25 parts by weight of DMS-S14 (commercial name, produced by GELESTInc.) containing the both-terminal polydimethyl siloxane silanol as itsmain component.

2) 0.1 parts by weight of SIP6560.0 (commercial name, produced by GELESTInc.) containing the methyltrimethoxysilane as its main component.

3) One part by weight (resin ratio: 50%) of a mixture of SIA0610.0(commercial name, produced by GELEST Inc.) containing the3-aminopropyltriethoxysilane as its main component and the ethanolsolution of the maleic anhydride.

4) 0.5 parts by weight of SIG5840.1 (commercial name, produced by GELESTInc.) containing the 3-glycidoxypropyltrimethoxysilane as its maincomponent.

After at a room temperature and a normal pressure, the gasket coremember produced in the above-described manner was heated to 90 degreesC. for 30 minutes, the gasket core member was rotated (300 rpm) on itsaxis with the coating solution having the above-described compositionbeing sprayed to the gasket core member from the side surface of thegasket core member which was rotating. Thereafter the coating solutionwas dried at 150 degrees C. for 30 minutes. Thereby the gasket wasformed. Thereafter to wash extra coating solution which remained on theproduced gasket, cleaning was performed with purified water having atemperature not less than 80 degrees C. The average thickness of acoating layer formed on the surface of the core member was about 8 μm.This gasket was the as the example 3.

Example 4

29 parts by weight of the silicone resin and one part by weight of thetin dioctyldilaurate were added to 66 parts by weight of the purifiedwater to prepare a coating solution. As the silicone resin, substancesshown below were mixed with one another by using the straight-chainsodium alkylbenzene sulfonate.

1) 25 parts by weight of YR3204 (commercial name, produced by MomentivePerformance Materials Japan, Limited Liability Company) containingpolyalkylphenylsiloxane having terminal silanol group as its maincomponent.

2) 0.1 parts by weight of TSL8178 (commercial name, produced byMomentive Performance Materials Japan, Limited Liability Company)containing the phenyltriethoxysilane as its main component.

3) One part by weight (resin ratio: 50%) of a mixture of TSL8331(commercial name, produced by Momentive Performance Materials Japan,Limited Liability Company) containing the 3-aminopropyltriethoxysilaneas its main component and the ethanol solution of the maleic anhydride.

4) 0.5 parts by weight of TSL8350 (commercial name, produced byMomentive Performance Materials Japan, Limited Liability Company)containing the 3-glycidoxypropyltrimethoxysilane as its main component.

After at a room temperature and a normal pressure, the gasket coremember produced in the above-described manner was heated to 90 degreesC. for 30 minutes, the gasket core member was rotated (300 rpm) on itsaxis with the coating solution having the above-described compositionbeing sprayed to the gasket core member from the side surface of thegasket core member which was rotating. Thereafter the coating solutionwas dried at 150 degrees C. for 30 minutes. Thereby the gasket wasformed. Thereafter to wash extra coating solution which remained on theproduced gasket, cleaning was performed with purified water having atemperature not less than 80 degrees C. The average thickness of acoating layer formed on the surface of the core member was about 8 μm.This gasket was set as the example 4.

Comparison Example 1

29 parts by weight of the silicone resin as in the case of the example 1and one part by weight of the tin dioctyldilaurate were added to 66parts by weight of the purified water to prepare a main agent.

In addition, 52 parts by weight of silicone rubber powder, and 2 partsby weight of the polyoxyethylenealkyl ether were added to 46 parts byweight of the purified water to prepare a fine powder liquid. As thesilicone rubber powder, silicone rubber powder KMP-600 (commercial name,produced by Shin-Etsu Chemical Industry Co., Ltd.) was used. Five partsby weight of the purified water and three parts by weight of the finepowder liquid were added to five parts by weight of the main agent, andthey were mixed with one another to prepare a coating solution.

After at a room temperature and a normal pressure, the gasket coremember produced in the above-described manner was heated to 90 degreesC. for 30 minutes, the gasket core member was rotated (300 rpm) on itsaxis with the coating solution having the above-described compositionbeing sprayed to the gasket core member from the side surface of thegasket core member which was rotating. Thereafter the coating solutionwas dried at 150 degrees C. for 30 minutes. Thereby the gasket wasformed. Thereafter to wash extra coating solution which remained on theproduced gasket, cleaning was performed with purified water having atemperature not less than 80 degrees C. The average thickness of acoating layer formed on the surface of the core member was about 8 μm.This gasket was set as the comparison example 1.

Comparison Example 2

29 parts by weight of the silicone resin as in the case of the example 1and one part by weight of the tin dioctyldilaurate were added to 66parts by weight of the purified water to prepare a main agent.

In addition 52 parts by weight of the silicone rubber powder KMP-600(commercial name, produced by Shin-Etsu Chemical Industry Co., Ltd.) and2 parts by weight of the polyoxyethylenealkyl ether were added to 46parts by weight of the purified water to prepare a fine powder liquid.

After five parts by weight of the purified water and two parts by weightof the fine powder liquid were added to six parts by weight of the mainagent, they were mixed with one another to prepare a coating solution.

After at a room temperature and a normal pressure, the gasket coremember produced in the above-described manner was heated to 90 degreesC. for 30 minutes, the gasket core member was rotated (300 rpm) on itsaxis with the coating solution having the above-described compositionbeing sprayed to the gasket core member from the side surface of thegasket core member which was rotating. Thereafter the coating solutionwas dried at 150 degrees C. for 30 minutes. Thereby the gasket wasformed. Thereafter to wash extra coating solution which remained on theproduced gasket, cleaning was performed with purified water having atemperature not less than 80 degrees C. The average thickness of acoating layer formed on the surface of the core member was about 8 μm.This gasket was set as the comparison example 2.

Comparison Example 3

29 parts by weight of the silicone resin as in the case of the example 1and one part by weight of the tin dioctyldilaurate were added to 66parts by weight of purified water to prepare a main agent.

In addition 52 parts by weight of the silicone rubber powder KMP-600(commercial name, produced by Shin-Etsu Chemical Industry Co., Ltd.),and 2 parts by weight of the polyoxyethylenealkyl ether were added to 46parts by weight of the purified water to prepare a fine powder liquid.

After five parts by weight of the purified water and one part by weightof the fine powder liquid were added to seven parts by weight of themain agent, they were mixed with one another to prepare a coatingsolution.

After at a room temperature and a normal pressure, the gasket coremember produced in the above-described manner was heated to 90 degreesC. for 30 minutes, the gasket core member was rotated (300 rpm) on itsaxis with the coating solution having the above-described compositionbeing sprayed to the gasket core member from the side surface of thegasket core member which was rotating. Thereafter the coating solutionwas dried at 150 degrees C. for 30 minutes. Thereby the gasket wasformed. Thereafter to wash extra coating solution which remained on theproduced gasket, cleaning was performed with purified water having atemperature not less than 80 degrees C. The average thickness of acoating layer formed on the surface of the core member was about 8 μm.This gasket was set as the comparison example 3.

Comparison Example 4

One part by weight of fluorine resin, 10 parts by weight of the siliconeresin, three parts by weight of urethane resin, 20 parts by weight oftalc fine powder (average particle diameter: approximately 3 μm), onepart by weight of N-methylpyrrolidone, one part by weight ofbutylcarbitol, and one part by weight of polyoxyethylenealkyl ether wereadded to 100 parts by weight of the purified water to prepare a coatingsolution. As the fluorine resin, Polyflon (product name, registeredtrademark) TFE (produced by Daikin Industries, Ltd.) containingtetrafluoroethylene as its main component was used. As the siliconeresin, SE1980 (product name, produced by Dow Corning Toray Co., Ltd.)which is aqueous silicon resin (aqueous silicone compound) was used. Asthe urethane resin, Rozan 1100 (product name, produced by Toyo PolymerCo., Ltd.) which is aqueous urethane resin was used.

As a silane coupling agent, TSL8310 (commercial name, produced byMomentive Performance Materials Japan, Limited Liability Company)containing vinyltrimethoxysilane as its main component was prepared.

After five parts by weight of the silane coupling agent was added to 95parts by weight of the main agent, both agents were mixed with eachother to prepare a coating solution.

After at a room temperature and a normal pressure, the gasket coremember produced in the above-described manner was heated to 90 degreesC. for 30 minutes, the gasket core member was rotated (300 rpm) on itsaxis with the coating solution having the above-described compositionbeing sprayed to the gasket core member from the side surface of thegasket core member which was rotating. Thereafter the coating solutionwas dried at 150 degrees C. for 30 minutes. Thereby the gasket wasformed. Thereafter to wash extra coating solution which remained on theproduced gasket, cleaning was performed with purified water having atemperature not less than 80 degrees C. The average thickness of acoating layer formed on the surface of the core member was about 10 μm.This gasket was set as the comparison example 4.

Experiment 1: Stability of Coating Solution

The stability of the coating solutions prepared in the examples 1through 4 and the comparison examples 1 through 4 were evaluated. Theappearances of the coating solutions after they were refrigerated forone month are as shown in table 1.

TABLE 1 Appearance Immediately after preparation After one-monthrefrigeration Example 1 White emulsion No change from appearanceimmediately after preparation Example 2 White emulsion No change fromappearance immediately after preparation Example 3 White emulsion Nochange from appearance immediately after preparation Example 4 Whiteemulsion No change from appearance immediately after preparationComparison White emulsion White precipitation is example 1 confirmed.Comparison White emulsion White precipitation is example 2 confirmed.Comparison White emulsion White precipitation is example 3 confirmed.Comparison White emulsion Grey precipitation is example 4 confirmed.

Experiment 2: Friction Coefficient Measurement Test

After the coating solutions prepared in the example 2 and the comparisonexample 1 were applied to an EPDM rubber sheet, having a size of 30mm×50 mm and a thickness of 2 mm, which was heated to 90 degrees C. for30 minutes with a brush, the coating solutions were dried at 150 degreesC. for 30 minutes. Thereafter the rubber sheet was left still for 24hours at a room temperature. By applying a load of 100 to 1000 g to therubber sheet, a stress generated when the rubber sheet was horizontallymoved on the glass plate at a speed of 1000 mm/minute was measured byusing the method in accordance with JIS K7125 and a friction tester(reciprocating wear tester Type: 30, produced by Shinto Science Ltd.),and a dynamic friction coefficient (μd) and a static frictioncoefficient (μs) were found. Table 2 shows the results.

TABLE 2 Load 100 g Load 500 g Load 1000 g μd μs μd μs μd μs Example 20.2 0.6 0.2 0.6 0.2 0.5 Comparison 0.1 0.3 0.1 0.3 0.1 0.2 example 1

Experiment 3: Sliding Resistance Measurement Test

As a material of outer cylinders for syringes, polypropylene (producedby Japan Polychem Corporation) was injection-molded to produce outercylinders for syringes having the configuration shown in FIG. 5. Thecylindrical portion of each outer cylinder for use in the syringe had aninner diameter of 23.5 mm and a length of 95 mm. The polypropylene(produced by Japan Polychem Corporation) was injection-molded to formplungers having the configuration shown in FIG. 5.

The outer cylinders for the syringes, the gaskets of the examples 1 and2 and the comparison examples 1 through 4, and the plungers wereassembled to form syringes.

The sliding resistance value of each syringe was measured by anautograph (model name: EZ-Test, manufactured by Shimadzu Corporation).More specifically, with the distal end of each syringe and the proximalend of the plunger fixed to a fixing portion of the autograph to whichthe object to be measured, the plungers were moved downward 60 mm at aspeed of 100 mm/minute to measure the initial sliding resistance valueand the maximum sliding resistance value (N). Table 3 shows the results.

As shown in table 3, the syringes using the gaskets of the examples 1and 2 and the comparison examples 1 through 4 were almost equal in theinitial sliding resistance value and maximum sliding resistance valuethereof. In addition, each of the syringes had a small differencebetween the initial sliding resistance value and maximum slidingresistance value thereof. Thus there is little fear that a liquidmedicine was discharged from the syringes in an amount more than apredetermined amount when the plunger was started to be pressed.Therefore the syringes were capable of discharging the liquid medicinesafely and accurately. Favorable results that the initial slidingresistance value and the maximum sliding resistance value were not morethan 10N were obtained.

In the experiment 2 in which a test system conforming to JIS K7125 wasadopted, comparing a rubber sheet formed by using the coating solution(example 1) not containing the solid fine particles and a rubber sheetformed by using the coating solution (comparison example 2) containingthe solid fine particles with each other, it was shown that the rubbersheet formed by using the coating solution containing the solid fineparticles had a lower friction coefficient and a higher slidingperformance than the rubber sheet formed by using the coating solutionnot containing the solid fine particles. But the results obtained fromthe sliding-measuring test conducted in the experiment 2 in which thegasket and the syringe were combined with each other indicate that thecoating solution containing the solid fine particles is not superior tothe coating solution not containing the solid fine particles, but thecoating solution not containing the solid fine particles had also afavorable sliding performance.

TABLE 3 High penetration Sliding resistance liquid seal- Surface value(N) Pressure ing perfor- roughness (μm) Maximum test mance Ra Rz Example1 5.3 7.4 Passed Passed 1.38 35.11 Example 2 5.9 7.3 Passed Passed 1.4743.93 Comparison 4.2 8.3 Passed Passed 3.09 102.87 example 1 Comparison4.5 6.7 Passed Passed 2.35 79.39 example 2 Comparison 5.6 6.9 PassedPassed 2.16 72.67 example 3 Comparison 9.3 13.1 Passed Passed 2.92 56.74example 4

The above-described outer cylinders for the syringes, the gaskets of theexample 1 and the comparison example 4, and the above-described plungerswere assembled to form syringes. Thereafter 40 mL of purified water wasinjected to each syringe barrel. After a sealing member was fitted onthe leading end of the syringe barrel to seal it and perform autoclavesterilization, sliding resistance values were measured by the autograph(model name: EZ-Test, manufactured by Shimadzu Corporation) in theabove-described manner. The initial sliding resistance value and themaximum sliding resistance value (N) were measured at a test speed of 20to 500 mm/minute. Table 4 shows the results.

As shown in table 4, it has been found that at a test speed lower than100 mm/minute, the syringe using the gasket of the example 1 had a lowersliding resistance value than the syringe using the gasket of thecomparison example 4 containing fine particles. Thus it has been foundthat the sliding performance of the former at a speed suitable forinjecting a medicine into the vein is more favorable than that of thelatter.

The number of samples in each test is set to 10, and numerical values intable 4 show the average of 10 samples.

TABLE 4 Maximum sliding resistance value (N) 20 30 50 100 200 500 mm/minmm/min mm/min mm/min mm/min mm/min Example 1 9.6 10.1 11.7 15.7 21.229.5 Comparison 10.2 11.9 12.5 15.6 19.2 23.9 example 4

As a material forming an outer cylinder for a syringe, the outercylinder for the syringe having the configuration shown in FIG. 5 wasformed by using glass (produced by Shiotani Glass Co., Ltd.). Thecylindrical portion of the outer cylinder for the syringe had an innerdiameter of 23 mm and a length of 76 mm. As a material forming aplunger, polypropylene (produced by Japan Polychem Corporation) wasinjection-molded to form the plunger having the configuration shown inFIG. 5.

The outer cylinder for the syringe, the gasket of the example 1, and theplunger were assembled to form the syringe. Thereafter 20 mL of purifiedwater was injected to the outer cylinder. As in the case of theabove-described manner, the sliding resistance value was measured by theautograph (model name: EZ-Test, manufactured by Shimadzu Corporation).More specifically, with the distal end of the syringe and the proximalend of the plunger fixed to the fixing portion of the autograph to whichan object to be measured, the plunger was moved downward 45 mm at speedsof 20, 50, 100, and 500 mm/minute to measure the maximum slidingresistance value (N). Table 5 shows the results.

TABLE 5 Maximum sliding resistance value (N) 20 50 100 500 mm/min mm/minmm/min mm/min Example 1 6.0 7.3 11.4 14.2

Experiment 4: Pressure Test Specified in Standard of Sterilized Syringe

As a material of outer cylinders for syringes, polypropylene (producedby Japan Polychem Corporation) was injection-molded to produce outercylinders for the syringes having the configuration shown in FIG. 5. Thecylindrical portion of each outer cylinder for use in the syringe had aninner diameter of 23.5 mm and a length of 95 mm. As a material formingplungers, polypropylene (produced by Japan Polychem Corporation) wasinjection-molded to form the plungers having the configuration shown inFIG. 5.

The outer cylinders for the syringes, the gaskets of the example 1 and 2and the comparison examples 1 through 4, and the plungers were assembledto form syringes.

A test was conducted for the above-described syringes in accordance withthe pressure test specified in the standard of the sterilized plasticsyringe barrel which can be immediately used as it is and disposed atone-time use (notified on Dec. 11, 1998 by Director of Pharmaceuticaland Medical safety Bureau in 1079 issue of Pharmaceutical Development).Table 3 shows the results.

The number of samples in the test was five. “Passed” was marked forexamples and comparison examples in which all of the five samples passedinspection.

Experiment 5: Test for Examining Sealing Performance of High PenetrationLiquid

As a material of outer cylinders for syringes, polypropylene (producedby Japan Polychem Corporation) was injection-molded to produce outercylinders for the syringes having the configuration shown in FIG. 5. Thecylindrical portion of each of the outer cylinders for use in thesyringes had an inner diameter of 23.5 mm and a length of 95 mm. As amaterial forming plungers, polypropylene (produced by Japan PolychemCorporation) was injection-molded to form the plungers having theconfiguration shown in FIG. 5.

The outer cylinders for the syringes, the gaskets of the example 1 and 2and the comparison examples 1 through 4, and the plungers were assembledto form syringes.

Thereafter by using “Ageless” (registered trademark) “Checker” (producedby Mitsubishi Gas Chemical Company) for use in a test for examining thesealing performance of a heat sealing portion made of a soft plasticpacking material, a sealing performance test was conducted. The syringeswere left overnight to visually observe liquid leak from the slidingportion of the gasket. Table 3 shows the results.

The number of samples in the test was five. “Passed” was marked forexamples and comparison examples in which all of the five samples passedinspection.

Experiment 6: Surface Roughness

The surface roughness of each of the gaskets of the example 1 and 2 andthe comparison examples 1 through 4 was measured. The measuring methodwas carried out in accordance with JIS B0601 (1994). Table 3 shows theresults.

Experiment 7: Fixation Test

Plates made of polypropylene (produced by Japan Polychem Corporation)each having a size of 50 mm×70 mm and a thickness of 2 mm were prepared.In addition, after a rubber sheet (having a size of 10 mm×50 mm,thickness of 15 mm) made of butyl rubber which was also used for thegasket core member was heated to 90 degrees C. for 30 minutes, each ofthe coating solutions used in the example 2 and the comparison example 1was sprayed to the rubber sheet and dried at 150 degrees C. for 30minutes to prepare specimens.

With each specimen sandwiched between the polypropylene plate and aniron plate, a coating surface of the specimen set at the side of thepolypropylene plate, and the specimen fixed with a clip, each specimenwas left overnight in a thermostatic bath whose temperature was 40degrees C., 60 degrees C., and 80 degrees C. and for 10, 20, and 30 daysin the thermostatic bath whose temperature was 60 degrees C. The degreeof fixation was measured by using an autograph (model name: EZ-Test,manufactured by Shimadzu Corporation). Table 6 shows the results.

As a material of outer cylinders for syringes, polypropylene (producedby Japan Polychem Corporation) was injection-molded to produce the outercylinders for syringes having the configuration shown in FIG. 5. Thecylindrical portion of each outer cylinder for use in the syringe had aninner diameter of 23.5 mm and a length of 95 mm. As a material formingplungers, polypropylene (produced by Japan Polychem Corporation) wasinjection-molded to form the plungers having the configuration shown inFIG. 5.

The outer cylinders for the syringes, the gaskets of the example 2 andthe comparison example 1, and the plungers were assembled to formsyringes. Thereafter each syringe was left overnight in a thermostaticbath whose temperature was 40 degrees C., 60 degrees C., and 80 degreesC. and for 10, 20, and 30 days in the thermostatic bath whosetemperature was 60 degrees C. To evaluate the degree of fixation of thegasket to the outer cylinder for the syringe, the initial slidingresistance value of each syringe was measured by using the autograph(model name: EZ-Test, manufactured by Shimadzu Corporation).Specifically, with the distal end of each syringe and the proximal endof the plunger fixed to the fixing portion of the autograph to which anobject to be measured, the plungers were moved downward 60 mm at a speedof 100 mm/minute to measure the initial sliding resistance value (N).Table 7 shows the results.

TABLE 6 Fixing strength (kg/5 cm2) 40 60 80 60 degrees C. degrees C.degrees C. degrees C. 10 20 30 one day days days days Example 2 1.3 1.41.5 2.1 1.5 1.6 Comparison 0 0 0 0 0 0 example 1

TABLE 7 Initial sliding resistance value (N) Time 40 60 80 when degreesdegrees degrees 60 degrees C. test C. C. C. 10 20 30 started one daydays days days Example 2 5.39 5.39 5.76 6.12 6.33 6.44 7.32 Comparison4.97 5.48 6.14 7.39 7.54 6.94 8.93 example 1

Comparing a rubber sheet formed by using the coating solution (example2) not containing the solid fine particles and a rubber sheet formed byusing the coating solution (comparison example 1) containing the solidfine particles with each other, it was shown that the rubber sheetformed by using the coating solution containing the solid fine particleshad a lower fixation degree than the rubber sheet formed by using thecoating solution not containing the solid fine particles. But from theinitial sliding resistance value obtained in the sliding-measuring testconducted by combining the gasket and the syringe with each other, theresults of the fixation test (table 6) indicate that the coatingsolution containing the solid fine particles is not superior to thecoating solution not containing the solid fine particles, but there isno difference between the fixation degree of the coating solution notcontaining the solid fine particles and the fixation degree of thecoating solution containing the solid fine particles.

Experiment 8: Test for Examining Insoluble Fine Particles.

As a material of outer cylinders for syringes, polypropylene (producedby Japan Polychem Corporation) was injection-molded to produce the outercylinders for the syringes having the configuration shown in FIG. 5. Thecylindrical portion of each outer cylinder for use in the syringe had aninner diameter of 23.5 mm and a length of 95 mm. As a material formingplungers, Polypropylene (produced by Japan Polychem Corporation) wasinjection-molded to form the plungers having the configuration shown inFIG. 5. The outer cylinders for the syringes, the gaskets of the example1 and the comparison example 1, and the plungers were assembled to formsyringes. Thereafter 40 mL of purified water was injected to eachsyringe barrel. After a sealing member was fitted on the leading end ofthe syringe barrel to seal it and perform autoclave sterilization, thenumber of insoluble fine particles in the purified water was measuredafter the syringe was intensely shook for 10 minutes. Table 8 shows theresults.

TABLE 8 Number (piece) of insoluble fine particles per syringe Not lessthan Not less than Not less than 5 μm 10 μm 25 μm Example 1 33 4 0Comparison 144 24 0 example 1

Experiment 9: Test for Examining Flow Rate Accuracy with Syringe Pump

By using a syringe pump (TE-331, produced by Terumo Corporation), theflow rate accuracy of the syringe was evaluated. As a material of outercylinders for syringes, polypropylene (produced by Japan PolychemCorporation) was injection-molded to produce the outer cylinders for thesyringes having the configuration shown in FIG. 5. The cylindricalportion of each outer cylinder for use in the syringe had an innerdiameter of 23.5 mm and a length of 95 mm. As a material formingplungers, polypropylene (produced by Japan Polychem Corporation) wasinjection-molded to form the plungers having the configuration shown inFIG. 5.

The outer cylinders for syringes, the gaskets of the example 1 and thecomparison example 1, and the plungers were assembled to form syringes.

Thereafter 40 mL of purified water was injected to each syringe barrel.After a sealing member was fitted on the leading end of the syringebarrel to seal it and perform autoclave sterilization, each syringe wasset on the syringe pump to discharge the purified water for eight hoursat a flow rate of 5 mL/hour. By using an electronic balance, the weightof the discharged purified water was measured at intervals of 30seconds. As a result, discharge amplitude results as shown in FIG. 6(example 1) and FIG. 7 (comparison example 1) were obtained. As apparentfrom FIGS. 6 and 7, it has been confirmed that the syringe of theexample 1 had smaller amplitude and more stable discharge than thecomparison example 7.

The gasket disclosed by way of example here includes a number ofaspects.

For example, the gasket has useful application with a syringe toliquid-tightly and slidably contact an inner surface of an outercylinder of the syringe. The gasket has a gasket body made of an elasticbody and a coating layer formed in a portion thereof which contacts atleast the syringe. The coating layer is composed of a compositioncontaining silicone resin which consists of a condensate of reactivesilicone resin having a terminal silanol group and which has a siloxanebond derived from the silanol group and does not contain solid fineparticles.

The gasket for use in the syringe has the coating layer disposed at theportion thereof which contacts the outer cylinder. The coating layer iscomposed of the composition containing the specific silicone resin.Therefore the coating layer has stable sliding performance withoutapplying a lubricant to the sliding surface of the gasket.

The coating layer of the gasket can be formed by using the reactivesilicone containing the terminal silanol group and the water-basedcoating agent containing the catalyst for curing the reactive siliconeand can be produced stably, easily, and securely.

As compared with the coating layer containing fine particles, thecoating layer of the gasket has a favorable sliding resistance valuewhen the gasket slides at a low speed and prevents the syringe and thegasket from sticking to each other during storage. Therefore in usingthe syringe, it is possible to smoothly move the gasket in its initialmovement and thus avoid a rapid injection and achieve injection at aconstant speed.

Even in a sucking operation to be often performed to check whether avessel has been secured, the possibility of the separation of the fineparticles from the gasket is not nil in the gasket having the coatinglayer containing fine particles. Because the fine particles are notcontained in an exemplary embodiment, the risk of the separation of thefine particles from the gasket is nil.

The embodiment of the gasket disclosed here can also be constructed withadditional aspects such as described below. For example, the gasket foruse in the syringe can be constructed so that the reactive silicone ispolydimethylsiloxane having a terminal silanol group. The reactivesilicone has the silanol group at both terminals thereof. Also, thecomposition contains a second silicone compound different from thesilicone resin having the siloxane bond. The second silicone compound isalkylalkoxysilane, phenylalkoxysilane, aminoalkylalkoxysilane orglycidoxyalkylalkoxysilane. The composition contains alkylalkoxysilaneor phenylalkoxysilane as a second silicone compound; and furthercontains aminoalkylalkoxysilane or/and glycidoxyalkylalkoxysilane as athird silicone compound. Additionally, the composition containsalkylalkoxysilane or phenylalkoxysilane as a second silicone compound;and further contains aminoalkylalkoxysilane as a third siliconecompound; and contains glycidoxyalkylalkoxysilane as a fourth siliconecompound. The silicone resin is hermosetting, and the coating layer canhave a thickness of 1 to 30 μm. The initial sliding resistance value ofthe coating layer is not more than a maximum value of a dynamic slidingresistance value thereof, and an outer cylinder made of plastics canalso be used. The syringe with which the gasket is usable comprises anouter cylinder, the gasket is slidably accommodated inside the outercylinder; and a plunger is either mounted on the gasket or is adapted tobe mounted on the gasket. The syringe can be filled with a liquidmedicine. The dynamic sliding resistance value of the gasket when thegasket slides at a low speed (100 mm/minute) inside the outer cylinderis not more than 20N. The outer cylinder of the syringe can be made ofplastics.

The detailed description above describes various aspects of a gasket anda syringe embodying the gasket. However it is to be understood that theinvention is not limited to the precise embodiment described andillustrated above. Various changes, modifications and equivalents couldbe effected by one skilled in the art without departing from the spiritand scope of the invention as defined in the appended claims. It isexpressly intended that all such changes, modifications and equivalentswhich fall within the scope of the claims are embraced by the claims.

The invention claimed is:
 1. A gasket for use in a syringe so formed asto liquid-tightly and slidably contact an inner surface of an outercylinder of said syringe, said gasket comprising a gasket body made ofan elastic body and a coating layer formed on a portion thereof whichcontacts at least said syringe, wherein said coating layer comprises acomposition containing a silicone resin which comprises a condensate ofa reactive silicone having a terminal silanol group at both terminalsthereof, and wherein the condensate contains a siloxane bond derivedfrom said silanol group, wherein said coating layer does not containsolid fine particles, wherein said composition contains analkylalkoxysilane or a phenylalkoxysilane as a second silicone compounddifferent from said silicone resin having said siloxane bond, anaminoalkylalkoxysilane or a glycidoxyalkylalkoxysilane as a thirdsilicone compound, and said gasket has a plunger which is mounted onsaid gasket body or is capable of being mounted thereon.
 2. The gasketfor use in the syringe according to claim 1, wherein said silicone resinis thermosetting.
 3. The gasket for use in the syringe according toclaim 1, wherein said coating layer has a thickness of 1 to 30 μm. 4.The gasket for use in the syringe according to claim 1, wherein aninitial sliding resistance value of said coating layer is not more thana maximum value of a dynamic sliding resistance value thereof.
 5. Asyringe comprising an outer cylinder; and the gasket according to claim1, which is slidably accommodated inside said outer cylinder.
 6. Thesyringe according to claim 5, wherein the syringe contains a liquidmedicine.
 7. The syringe according to claim 5, wherein a dynamic slidingresistance value of said gasket when said gasket slides at a low speedof 100 mm/minute inside said outer cylinder is not more than 20 N. 8.The gasket for use in the syringe according to claim 1, wherein saidreactive silicone having the terminal silanol group at both terminalsthereof is both-terminal polydimethylsiloxane silanol.
 9. The gasket foruse in the syringe according to claim 1, wherein said alkylalkoxysilaneis methyltrimethoxysilane.
 10. The gasket for use in the syringeaccording to claim 1, wherein said aminoalkylalkoxysilane is3-aminopropyltriethoxysilane.
 11. The gasket for use in the syringeaccording to claim 1, wherein said glycidoxyalkylalkoxysilane is3-glycidoxypropyltrimethoxysilane.
 12. The gasket for use in the syringeaccording to claim 1, wherein said reactive silicone having the terminalsilanol group at both terminals thereof is both-terminalpolydimethylsiloxane silanol, said aminoalkylalkoxysilane is3-aminopropyltriethoxysilane and said glycidoxyalkylalkoxysilane is3-glycidoxypropyltrimethoxysilane.
 13. The gasket for use in the syringeaccording to claim 1, wherein said coating layer is formed from acoating solution containing components composing the reactive siliconehaving the terminal silanol group at both terminals thereof, thealkylalkoxysilane and the aminoalkylalkoxysilane or theglycidoxyalkylalkoxysilane dispersed and suspended in purified water,and the coating layer is obtained by applying the coating solution to asurface of the gasket and thereafter curing the coating solution. 14.The gasket for use in the syringe according to claim 1, wherein saidcomposition contains said aminoalkylalkoxysilane as said third siliconecompound and said glycidoxyalkylalkoxysilane as a fourth siliconecompound.